Left untreated, human immunodeficiency virus (HIV) replicates at a rapid
rate, with the eventual production of billions of new virus particles per
day. Given the propensity of HIV to mutate, the possibility exists that each
newly produced virus contains at least 1 new mutation. Thus, from a darwinian
perspective, ongoing viral replication in the presence of therapy should result
in the rapid selection of drug resistance mutations and subsequent virologic
rebound. These basic principles have provided the theoretical context for
the "hit hard" therapeutic approach to HIV disease.1
According to current treatment guidelines,1- 3
complete viral suppression should be the goal of therapy. Once therapy is
initiated, plasma viremia, as measured by the concentration of viral RNA in
plasma, should decrease to below the level of detection using the most sensitive
assay available.2,3 Persistent
viremia suggests ongoing viral replication and treatment failure. The findings
from 2 articles in this issue of THE JOURNAL raise questions about this conceptual
framework, and based on data from the 2 studies, it may be argued that "complete"
viral suppression may not be a prerequisite for durable treatment benefit.